The morphological development of the proventriculus of Dandarawi chick: Light and electron microscopical studies.

This study was carried out on 40 chick embryos collected from incubated eggs of Dandarawi chicken (Gallus gallus domesticus) on the 5th to 19th incubation day (27 to 45 Hamburger and Hamilton, H&H stages). In addition, 15 chicks were collected on the day of hatching (stage 46 H&H), one week and two weeks post-hatching to demonstrate the histological, histochemical, and electron microscopic developmental changes of the proventriculus (of the digestive tract). Histologically, the proventriculus was observed as a narrow tube at 27 H&H stage. It was lined by pseudostratified columnar epithelium through 27-39 H&H stages and from the stage 43 till post-hatching, it was lined by simple columnar epithelium. The Lamina muscularis mucosa could be identified at stage 43. The proventricular glands were detected firstly at stage 31 and branching at stage 35. Histochemically, the surface epithelium and proventricular glands reacted positively to PAS, alcian blue and bromophenol blue from stage 31 till maturity. The glands displayed an apocrine mode of secretion at stage 39 and their cytoplasm contained abundant mitochondria, RER, secretory granules, and lipid droplets. Enteroendocrine cells could be observed among the glandular and surface epithelium at stage 45 H&H. The interstitial tissue contained fibroblasts and telocytes. The telocytes were firstly detected at stage 35 H&H and composed of a cell body and two long cell processes called telopodes. The tunica muscularis differentiated into three layers of smooth muscle fibers at stage 37 H&H. The cellular and stromal organizations of the proventriculus and their relations to the development and function were discussed.

Microbial regulation of the L cell transcriptome.

L cells are an important class of enteroendocrine cells secreting hormones such as glucagon like peptide-1 and peptide YY that have several metabolic and physiological effects. The gut is home to trillions of bacteria affecting host physiology, but there has been limited understanding about how the microbiota affects gene expression in L cells. Thus, we rederived the reporter mouse strain, GLU-Venus expressing yellow fluorescent protein under the control of the proglucagon gene, as germ-free (GF). Lpos cells from ileum and colon of GF and conventionally raised (CONV-R) GLU-Venus mice were isolated and subjected to transcriptomic profiling. We observed that the microbiota exerted major effects on ileal L cells. Gene Ontology enrichment analysis revealed that microbiota suppressed biological processes related to vesicle localization and synaptic vesicle cycling in Lpos cells from ileum. This finding was corroborated by electron microscopy of Lpos cells showing reduced numbers of vesicles as well as by demonstrating decreased intracellular GLP-1 content in primary cultures from ileum of CONV-R compared with GF GLU-Venus mice. By analysing Lpos cells following colonization of GF mice we observed that the greatest transcriptional regulation was evident within 1 day of colonization. Thus, the microbiota has a rapid and pronounced effect on the L cell transcriptome, predominantly in the ileum.

Glucagon-like peptide-1 is co-localized with neurotensin in the chicken ileum.

Glucagon-like peptide (GLP)-1 and neurotensin (NT) are distributed throughout the chicken ileum. Here, we attempt to determine if GLP-1 and NT co-localize in the chicken ileum by using immunofluorescence, immunocytochemistry and in situ hybridization techniques. Three types of enteroendocrine cells, GLP-1+/NT+, GLP-1+/NT- and GLP-1-/NT+ cells, were detected in the mucosal epithelium by the double immunofluorescence method. The ratio of GLP-1+/NT+ cells at the crypts in the distal ileum was significantly higher than that in the proximal ileum. The ratios of the three cell types were similar along the crypt-villous axis in the proximal ileum but the percentage of GLP-1+/NT+ cells significantly decreased at the middle part of villi relative to crypts and the bottom part of villi in the distal ileum. Enteroendocrine cells that were immunoreactive to both GLP-1 and NT peptides and showed both proglucagon and NT precursor mRNA signals were found in the crypts of the distal ileum but not in the villous epithelium. The results from performing an immunocytochemical method with colloidal gold indicated that the GLP-1 content within GLP-1+/NT+ cell secretory granules decreased stepwise from the crypt to the middle part of the villus but the NT content in these granules increased in this direction. These findings reveal that the cells producing both GLP-1 and NT are mainly localized in the crypts of the chicken ileum but these endocrine cells specialize in NT-producing cells at the villous epithelium of the distal ileum.

Neurotensin Is Coexpressed, Coreleased, and Acts Together With GLP-1 and PYY in Enteroendocrine Control of Metabolism.

The 2 gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are well known to be coexpressed, costored, and released together to coact in the control of key metabolic target organs. However, recently, it became clear that several other gut hormones can be coexpressed in the intestinal-specific lineage of enteroendocrine cells. Here, we focus on the anatomical and functional consequences of the coexpression of neurotensin with GLP-1 and PYY in the distal small intestine. Fluorescence-activated cell sorting analysis, laser capture, and triple staining demonstrated that GLP-1 cells in the crypts become increasingly multihormonal, ie, coexpressing PYY and neurotensin as they move up the villus. Proglucagon promoter and pertussis toxin receptor-driven cell ablation and reappearance studies indicated that although all the cells die, the GLP-1 cells reappear more quickly than PYY- and neurotensin-positive cells. High-resolution confocal fluorescence microscopy demonstrated that neurotensin is stored in secretory granules distinct from GLP-1 and PYY storing granules. Nevertheless, the 3 peptides were cosecreted from both perfused small intestines and colonic crypt cultures in response to a series of metabolite, neuropeptide, and hormonal stimuli. Importantly, neurotensin acts synergistically, ie, more than additively together with GLP-1 and PYY to decrease palatable food intake and inhibit gastric emptying, but affects glucose homeostasis in a more complex manner. Thus, neurotensin is a major gut hormone deeply integrated with GLP-1 and PYY, which should be taken into account when exploiting the enteroendocrine regulation of metabolism pharmacologically.

Ileal Interposition in Rats with Experimental Type 2 Like Diabetes Improves Glycemic Control Independently of Glucose Absorption.

Bariatric operations in obese patients with type 2 diabetes often improve diabetes before weight loss is observed. In patients mainly Roux-en-Y-gastric bypass with partial stomach resection is performed. Duodenojejunal bypass (DJB) and ileal interposition (IIP) are employed in animal experiments. Due to increased glucose exposition of L-cells located in distal ileum, all bariatric surgery procedures lead to higher secretion of antidiabetic glucagon like peptide-1 (GLP-1) after glucose gavage. After DJB also downregulation of Na(+)-d-glucose cotransporter SGLT1 was observed. This suggested a direct contribution of decreased glucose absorption to the antidiabetic effect of bariatric surgery. To investigate whether glucose absorption is also decreased after IIP, we induced diabetes with decreased glucose tolerance and insulin sensitivity in male rats and investigated effects of IIP on diabetes and SGLT1. After IIP, we observed weight-independent improvement of glucose tolerance, increased insulin sensitivity, and increased plasma GLP-1 after glucose gavage. The interposed ileum was increased in diameter and showed increased length of villi, hyperplasia of the epithelial layer, and increased number of L-cells. The amount of SGLT1-mediated glucose uptake in interposed ileum was increased 2-fold reaching the same level as in jejunum. Thus, improvement of glycemic control by bariatric surgery does not require decreased glucose absorption.

Alterations of rat stomach endocrine cells under renovascular hypertension.

PURPOSE: The aim of the present study was to perform immunohistochemical and ultrastructural analysis of gastrin-, synaptophysin (SY)- and atrial natriuretic peptide (ANP)-positive cells in the pylorus of "two kidney, one clip" (2K1C) renovascular hypertension model in rats. MATERIAL/METHODS: In order to identify neuroendocrine (NE) cells, immunohistochemical reactions were performed with the use of specific antibodies against gastrin, SY and ANP. Gastric NE cells were also examined using an electron microscope. RESULTS: The present study revealed a twofold increase in the number of gastrin- and SY-positive cells and a significant decrease in the number of ANP-immunoreactive (IR) cells in the pyloric mucosa of 2K1C rats. Test results obtained with an electron microscope confirmed a change in the activity of the stomach endocrine cells of hypertensive rats. CONCLUSIONS: Immunohistochemical and ultrastructural investigations demonstrated the impact of renovascular hypertension on the neuroendocrine system in the rat stomach. The changes in the total number and ultrastructure of DNES cells proved their undeniable role in the modulation of gastric dysfunction, as a consequence of deregulation of homeostasis-maintaining systems.

An enteroendocrine cell-enteric glia connection revealed by 3D electron microscopy.

The enteroendocrine cell is the cornerstone of gastrointestinal chemosensation. In the intestine and colon, this cell is stimulated by nutrients, tastants that elicit the perception of flavor, and bacterial by-products; and in response, the cell secretes hormones like cholecystokinin and peptide YY--both potent regulators of appetite. The development of transgenic mice with enteroendocrine cells expressing green fluorescent protein has allowed for the elucidation of the apical nutrient sensing mechanisms of the cell. However, the basal secretory aspects of the enteroendocrine cell remain largely unexplored, particularly because a complete account of the enteroendocrine cell ultrastructure does not exist. Today, the fine ultrastructure of a specific cell can be revealed in the third dimension thanks to the invention of serial block face scanning electron microscopy (SBEM). Here, we bridged confocal microscopy with SBEM to identify the enteroendocrine cell of the mouse and study its ultrastructure in the third dimension. The results demonstrated that 73.5% of the peptide-secreting vesicles in the enteroendocrine cell are contained within an axon-like basal process. We called this process a neuropod. This neuropod contains neurofilaments, which are typical structural proteins of axons. Surprisingly, the SBEM data also demonstrated that the enteroendocrine cell neuropod is escorted by enteric glia--the cells that nurture enteric neurons. We extended these structural findings into an in vitro intestinal organoid system, in which the addition of glial derived neurotrophic factors enhanced the development of neuropods in enteroendocrine cells. These findings open a new avenue of exploration in gastrointestinal chemosensation by unveiling an unforeseen physical relationship between enteric glia and enteroendocrine cells.

Ultrastructural study on colocalization of glucagon-like peptide (GLP)-1 with GLP-2 in chicken intestinal L-cells.

Colocalization of glucagon-like peptide (GLP)-1 with GLP-2 in L-cells was investigated in the chicken ileum by using double immunofluorescent and immunocytochemical techniques. Ultrastructural features of L-cells were also clarified in this study. L-cells showing immunoreactivity for both GLP-1 and GLP-2 were distributed in the whole ileum. They showed comma-like or flask-like shape and were located in epithelium of crypts and lower part of intestinal villi. L-cells showing GLP-1-immunoreactivity only were found in epithelium of lower and middle parts of intestinal villi. Transmission electron microscopy indicated that L-cells identified by colloidal gold-labeled immunocytochemistry were covered apically with microvilli, open-type and contained many secretory granules in their perikarya. These secretory granules without halo were round to oval in shape and showed moderate electron density. The longest and shortest diameters of secretory granules were 355 ± 62 nm (mean ± SD) and 287 ± 48 nm, respectively. Double labeling immunocytochemistry using two different sizes of particles (6 and 12 nm in diameter) of colloidal gold revealed that GLP-1 colocalized with GLP-2 in the same secretory granules. This study advances new morphological data about the endocrine system of the chicken small intestine.

Cellular bases for interactions between immunocytes and enteroendocrine cells in the intestinal mucosal barrier of rhesus macaques.

The roles of the interactions between nervous, endocrine, and immune systems have been well established in human health and diseases. At present, little is known about the cellular bases for neural-endocrine-immune networks in the gastrointestinal mucosa. In the current study, duodenum, jejunum, ileum, cecum, colon, and rectum autopsies from 15 rhesus macaques and endoscopic duodenal biopsies from 12 rhesus macaques were collected, and the spatial relationships between the endocrine cells and immune cells in the intestinal mucosa were examined by transmission electron microscopy. Eight types of enteroendocrine cells similar to human enterochromaffin cells (EC), D1, G, I, K, L, N, and S cells were found to lie within a one-cell-size distance from immunocytes, in particular the eosinophils in the epithelia or lamina propria. Close apposition of large areas of plasma membranes between many types of enteroendocrine cells and immunocytes, especially between EC, K, S cells and eosinophils, were observed in the epithelia for the first time. These data indicate that complex interactions occur between diverse types of enteroendocrine cells and various immune cells through paracrine mechanisms or via mechanisms dependent on cell-to-cell contact; such interactions might play key roles in maintaining the gut mucosal barrier integrity of rhesus macaques.

Cell Lineage metastability in Gfi1-deficient mouse intestinal epithelium.

Elucidating the mechanisms determining multipotent progenitor cell fate remains a fundamental project of contemporary biology. Various tissues of mice and men with defects in the zinc-finger transcriptional repressor Gfi1 have dramatic perturbations in the proportions of their differentiated cell types. In Gfi1-deficient intestinal epithelium there is a shift from mucous and Paneth towards enteroendocrine cells, leading to the proposal that Gfi1 functions in the allocation of the progeny derived from a hypothetical common granulocytic progenitor. However, studies of clones have yielded no evidence of such a common progenitor prompting us to investigate alternate mechanisms explaining the Gfi1-deficient phenotype. We report that mucous and Paneth but not enteroendocrine lineage cells normally express Gfi1. Sporadic mucous and Paneth lineage cells in the crypts of Gfi1-deficient mice aberrantly express the pro-enteroendocrine transcription factor Neurog3, indicating that stable repression of Neurog3 in these lineages requires Gfi1. Importantly, we also find mucous and Paneth lineage cells in various stages of cellular reprogramming into the enteroendocrine lineage in Gfi1-deficient mice. We propose that mucous and Paneth cell lineage metastability, rather than reallocation at the level of a hypothetical common granulocytic progenitor, is responsible for the shifts in cell type proportions observed in Gfi1-deficient intestinal epithelium.

Chlamydia trachomatis antigens in enteroendocrine cells and macrophages of the small bowel in patients with severe irritable bowel syndrome.

BACKGROUND: Inflammation and immune activation have repeatedly been suggested as pathogentic factors in irritable bowel syndrome (IBS). The driving force for immune activation in IBS remains unknown. The aim of our study was to find out if the obligate intracellular pathogen Chlamydia could be involved in the pathogenesis of IBS. METHODS: We studied 65 patients (61 females) with IBS and 42 (29 females) healthy controls in which IBS had been excluded. Full thickness biopsies from the jejunum and mucosa biopsies from the duodenum and the jejunum were stained with a monoclonal antibody to Chlamydia lipopolysaccharide (LPS) and species-specific monoclonal antibodies to C. trachomatis and C. pneumoniae. We used polyclonal antibodies to chromogranin A, CD68, CD11c, and CD117 to identify enteroendocrine cells, macrophages, dendritic, and mast cells, respectively. RESULTS: Chlamydia LPS was present in 89% of patients with IBS, but in only 14% of healthy controls (p < 0.001) and 79% of LPS-positive biopsies were also positive for C. trachomatis major outer membrane protein (MOMP). Staining for C. pneumoniae was negative in both patients and controls. Chlamydia LPS was detected in enteroendocrine cells of the mucosa in 90% of positive biopsies and in subepithelial macrophages in 69% of biopsies. Biopsies taken at different time points in 19 patients revealed persistence of Chlamydia LPS up to 11 years. The odds ratio for the association of Chlamydia LPS with presence of IBS (43.1; 95% CI: 13.2-140.7) is much higher than any previously described pathogenetic marker in IBS. CONCLUSIONS: We found C. trachomatis antigens in enteroendocrine cells and macrophages in the small bowel mucosa of patients with IBS. Further studies are required to clarify if the presence of such antigens has a role in the pathogenesis of IBS.

Ultrastructure of the Alabama argillacea (Hübner) (Lepidoptera: Noctuidae) midgut.

The insect midgut has ultimately been the focus of researches tempting to control insect pests because alterations in the insect gut may affect not only its development, but also physiological events such as nutrient absorption and transformation. The objective of the present work was to describe morphologically, histochemically, and ultrastructurally the larva midgut of Alabama argillacea (Hübner) (Lepidoptera: Noctuidae), a cotton key pest in Brazil. Light and electronic transmission microscopy was used to obtain images from midgut sections of late fourth-instar larvae of A. argillacea. In general, the morphology, histochemistry, and ultrastructure characteristics of A. argillacea midgut follow that described in the literature for other lepidopteran species. However, the results showed a mitochondrial polymorphism and branched microvilli, which suggest an ultrastrucutural and physiological modification possibly associated with a high absorption and secretion activity by the columnar cells of this species. This intense activity may favor a faster response related to the action of ingested microbial agents and/or toxins, and can explain the high susceptibility of A. argillacea to the agents of control such as the toxin of Bacillus thuringiensis.

Characterization of obestatin- and ghrelin-producing cells in the gastrointestinal tract and pancreas of rats: an immunohistochemical and electron-microscopic study.

Both ghrelin and obestatin are derived from preproghrelin by post-translational processing. We have morphologically characterized the cells that produce obestatin and ghrelin in new-born and adult Sprague-Dawley rats that were freely fed, fasted, or subjected to gastric bypass surgery or reserpine treatment. Tissue samples collected from the gastrointestinal tract and pancreas were examined by double-immunofluorescence staining, immunoelectron microscopy, and conventional electron microscopy. Obestatin was present in the stomach, duodenum, jejunum, colon, and pancreas. In the stomach, differences were noted in the development of obestatin- and preproghrelin-immunreactive (IR) cells on the one hand and ghrelin-IR cells on the other, particularly 2 weeks after birth. Preproghrelin- and obestatin-IR cells were more numerous than ghrelin-IR cells in the stomach, suggesting the lack of ghrelin in some A-like cells. Most obestatin-producing cells in the stomach were distributed in the basal part of the oxyntic mucosa; these cells co-localized with chromogranin A (pancreastatin) and vesicle monoamine transporters type 1 and 2, but not with serotonin or histidine decarboxylase. Immunoelectron microscopy revealed the obestatin- and ghrelin-producing cells to be A-like cells, characterized by numerous highly electron-dense granules containing ghrelin and obestatin. Some granules exhibited an even electron density with thin electron-lucent halos, suggestive of monoamines. Feeding status, gastric bypass surgery, and reserpine treatment had no obvious effect on the A-like cells. In the pancreas, obestatin was present in the peripheral part of the islets, with a distribution distinct from that of glucagon-producing A cells, insulin-producing beta cells, and cells producing pancreatic polypeptide Y. Thus, obestatin and ghrelin co-localize with an anticipated monoamine in A-like cells in the stomach, and obestatin is found in pancreatic islets.

[Irritated bowel syndrome: clinico-morphological types].

One hundred twenty eight patients with irritated bowel syndrome (IBS) were included in the study and divided into two equal groups. Group one consisted of patients with type II IBS (without atrophic changes in the colon mucosa, CM); group II consisted of patients with type II IBS (with atrophic changes in the CM); the control group consisted of 24 practically healthy individuals. All the subjects, including the healthy ones, were examined using clinical, endoscopic, immunohistochemical methods, and electron microscopy. The study found that the development of type IIBS was connected with hyperplasia and hyperfunction of serotonin-producing cells with intensification of apoptosis. The number of colonocytes with nuclei that are immunopositive to D1 cycline increases, and the number of colonocyte nuclei that are immunopositive to proliferating cell nuclear antigen decreases. The onset of type II IBS is associated with hyperplasia and hyperfunction of all apudocyte populations, including those producing melatonin and serotonin, and simultaneous reduction of the number and functional exhaustion of VIP-producing and mast cells. Colonocyte apoptosis intensifies; their proliferative potential decreases.

Midgut epithelial endocrine cells are a rich source of the neuropeptides APSGFLGMRamide (Cancer borealis tachykinin-related peptide Ia) and GYRKPPFNGSIFamide (Gly1-SIFamide) in the crabs Cancer borealis, Cancer magister and Cancer productus.

Over a quarter of a century ago, Mykles described the presence of putative endocrine cells in the midgut epithelium of the crab Cancer magister (Mykles, 1979). In the years that have followed, these cells have been largely ignored and nothing is known about their hormone content or the functions they play in this species. Here, we used a combination of immunohistochemistry and mass spectrometric techniques to investigate these questions. Using immunohistochemistry, we identified both SIFamide- and tachykinin-related peptide (TRP)-like immunopositive cells in the midgut epithelium of C. magister, as well as in that of Cancer borealis and Cancer productus. In each species, the SIFamide-like labeling was restricted to the anterior portion of the midgut, including the paired anterior midgut caeca, whereas the TRP-like immunoreactivity predominated in the posterior midgut and the posterior midgut caecum. Regardless of location, label or species, the morphology of the immunopositive cells matched that of the putative endocrine cells characterized ultrastructurally by Mykles (Mykles, 1979). Matrix-assisted laser desorption/ionization-Fourier transform mass spectrometry identified the peptides responsible for the immunoreactivities as GYRKPPFNGSIFamide (Gly1-SIFamide) and APSGFLGMRamide [Cancer borealis tachykinin-related peptide Ia (CabTRP Ia)], respectively, both of which are known neuropeptides of Cancer species. Although the function of these midgut-derived peptides remains unknown, we found that both Gly1-SIFamide and CabTRP Ia were released when the midgut was exposed to high-potassium saline. In addition, CabTRP Ia was detectable in the hemolymph of crabs that had been held without food for several days, but not in that of fed animals, paralleling results that were attributed to TRP release from midgut endocrine cells in insects. Thus, one function that midgut-derived CabTRP Ia may play in Cancer species is paracrine/hormonal control of feeding-related behavior, as has been postulated for TRPs released from homologous cells in insects.

Changes of gastrointestinal argyrophil endocrine cells in the COLO205 tumor-implanted Balb/c-nu/nu mice.

The regional distributions and frequencies of argyrophil endocrine cells in gastrointestinal (GI) tract of Balb/c-nu/ nu mouse were studied using Grimelius silver stain after abdominal subcutaneous implantation of COLO205. The experimental animals were divided into two groups, one is non-implanted group (Sham) and the other is COLO205- implanted group. Samples were collected from GI tract (fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum) at 21 days after implantation of COLO205 cells (1 x 10(6) cell/mouse). In this study, argyrophil cells were detected throughout the entire GI tract with various frequencies regardless of implantation. Most of these argyrophil cells in the mucosa of GI tract were generally spherical or spindle in shape (open type cell) while cells showing round in shape (close type cell) were found occasionally in gastric and/or intestinal gland regions. The regional distributions of argyrophil cells in COLO205 were similar to those of Sham. However, significant decreases of argyrophil cells were detected in COLO205 compared to those of Sham except for the jejunum and ileum. In the jejunum and ileum, argyrophil cells in COLO205 showed similar frequencies compared to those of Sham. In the pylorus, the most dramatically decreasement of argyrophil cells were detected in COLO205 compared to that of Sham. Implantation of COLO205 tumor cell line induced severe quantitative changes of argyrophil cell density, and the abnormality in density of GI endocrine cells may contribute to the development of gastrointestinal symptoms such as anorexia and indigestion, frequently encountered in patients with cancer.

Endocrine and exocrine secretion of leptin by the gastric mucosa.

Leptin is a hormone that plays important roles in nutritional status and in obesity. By means of immunocytochemistry, two populations of leptin-secreting cells were found in the lower half of the gastric mucosa. One consists of numerous large cells located around the gastric pits, the Chief epithelial cells, whereas the second refers to much smaller cells, strongly stained, few in number, and scattered between the gastric pits, the endocrine cells. By double immunostaining, leptin and pepsinogen were colocalized in the Chief cells, whereas the endocrine cells were positive only for leptin. Immunoelectron microscopy showed that leptin is present along the rough endoplasmic reticulum-Golgi-granules secretory pathways of the Chief and endocrine cells. On the other hand, leptin-receptor (long and short forms) immunolabelings, although absent in the gastric epithelial cell plasma membranes, were present in enterocytes at the level of their apical and basolateral membranes. Duodenal, jejunal, and ileal enterocytes displayed similar labelings for the leptin receptor. Thus, exocrine and endocrine secretions of leptin together with the presence of leptin receptors on enterocyte plasma membranes constitute a gastroenteric axis that coordinates the role played by leptin in the digestive tract.

Immunohistochemical characterization of the distribution of galectin-4 in porcine small intestine.

Galectins are an evolutionarily conserved family of 15 different lectins found in various combinations in virtually every type of animal cell. One of the primary galectins expressed in intestinal epithelium is galectin-4, a tandem-repeat galectin with two carbohydrate-recognition domains in a single polypeptide chain. In the current study, we produced an anti-galectin-4 monoclonal antibody (MAb) for determining the distribution of galectin-4 in porcine small intestine to enhance our understanding of where galectin-4 performs its functions in the small intestine. In immunohistochemistry studies, this MAb detected galectin-4 primarily in the cytoplasm of absorptive epithelial cells lining intestinal villi. Mature epithelial cells at the villous tips stained the most intensely with this MAb, with progressively less intense staining observed along the sides of villi and into the crypts. In addition to its cytoplasmic localization, galectin-4 was also associated with nuclei in villous tip cells, indicating that some galectin-4 may migrate to the nucleus during terminal maturation of these cells. In intestinal crypts, a specific subset of cells, which may be enteroendocrine cells, expressed galectin-4 at a relatively high level. Galectin-4 distribution patterns were similar in all three regions (duodenum, jejunum, and ileum) of porcine small intestine.

Changes of gastrointestinal argyrophil endocrine cells in the COLO205 tumor-implanted Balb/c-nu/nu mice

The regional distributions and frequencies of argyrophil endocrine cells in gastrointestinal (GI) tract of Balb/c-nu/ nu mouse were studied using Grimelius silver stain after abdominal subcutaneous implantation of COLO205. The experimental animals were divided into two groups, one is non-implanted group (Sham) and the other is COLO205-implanted group. Samples were collected from GI tract (fundus, pylorus, duodenum, jejunum, ileum, cecum, colon and rectum) at 21 days after implantation of COLO205 cells (1x10(6) cell/mouse). In this study, argyrophil cells were detected throughout the entire GI tract with various frequencies regardless of implantation. Most of these argyrophil cells in the mucosa of GI tract were generally spherical or spindle in shape (open type cell) while cells showing round in shape (close type cell) were found occasionally in gastric and/or intestinal gland regions. The regional distributions of argyrophil cells in COLO205 were similar to those of Sham. However, significant decreases of argyrophil cells were detected in COLO205 compared to those of Sham except for the jejunum and ileum. In the jejunum and ileum, argyrophil cells in COLO205 showed similar frequencies compared to those of Sham. In the pylorus, the most dramatically decreasement of argyrophil cells were detected in COLO205 compared to that of Sham. Implantation of COLO205 tumor cell line induced severe quantitative changes of argyrophil cell density, and the abnormality in density of GI endocrine cells may contribute to the development of gastrointestinal symptoms such as anorexia and indigestion, frequently encountered in patients with cancer.

Ghrelin expression and actions: a novel peptide for an old cell type of the diffuse endocrine system.

Ghrelin is a gastric peptide involved in food intake control and growth hormone release. Its cell localization has been defined in distinct ghrelin cells of the gastric mucosa in humans and other mammals. Ghrelin production was also described in a number of other sites of the diffuse endocrine system, including the pituitary, thyroid, lung, pancreas, adrenal gland, and intestine. In addition, ghrelin cells were identified early during fetal life and in the placenta and gonads. Finally, endocrine growths and tumors of the diffuse endocrine system may present ghrelin-producing cells, and in a few cases high levels of circulating ghrelin were reported. Besides its well-defined orexigenic role, ghrelin is likely to exert a local paracrine role similar to other brain-gut axis hormones. This review aims to summarize recent data on ghrelin cell distribution in the diffuse endocrine system and discuss local and general ghrelin function during development, adulthood, and endocrine tumor development.